期刊
BIOLOGICAL PSYCHIATRY
卷 66, 期 11, 页码 997-1004出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2009.07.008
关键词
Cognition; COMT; prefrontal cortex; prepulse inhibition; synonymous COMT rs4818C/G polymorphism; tolcapone
资金
- University of Crete Research Funds Account [ELKE 1348]
- Manasaki scholarship
- Propondis Foundation
Background: The functional catechol-O-methyltransferase (COMT) valine158methionine (va1158met) polymorphism determines pre pulse inhibition (PPI) levels and working memory performance and the effects of tolcapone on these functions. Here, we explored the effects of the synonymous COMT rs4818 C/G polymorphism and tolcapone on PPI and working memory. Methods: Thirteen G/G (low prefrontal cortex [PFC] dopamine [DA]) and 12 C/C (high PFC DA) healthy male subjects entered and completed the study. Subjects participated in two weekly sessions associated with either acute oral tolcapone (200 mg) or placebo according to a balanced, crossover, double-blind design. Prepulse inhibition was assessed with 5 dB and 15 dB above background prepulses at 30-msec, 60-msec, and 120-msec intervals. Subjective mood and working memory performance (n-back and letter-number sequencing) were also assessed. Results: Prepulse inhibition was lower and reaction time in the n-back was slower in the G/G compared with the C/C group in the placebo condition. Tolcapone increased PPI and improved performance in both working memory tasks in the G/G group only. Baseline startle was greater in the C/C group and was not affected by tolcapone. Mood profile was worse in the C/C group and tended to deteriorate with tolcapone. Status of val158met alone could not explain these results. Conclusions: Catechol-O-methyltransferase haplotype analyses are essential in future research. Prepulse inhibition and working memory may both relate to PFC DA levels according to an inverted U-shaped curve function. Tolcapone could be potentially useful in the treatment of conditions with deficient sensorimotor gating and working memory such as schizophrenia and prodromal states but only in a genotype-specific manner.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据